Skull defect increases the tumor treating fields strength without detrimental thermogenic effect: A computational simulating research.

BACKGROUND: Tumor treating fields (TTFields) is an FDA-approved adjuvant therapy for glioblastoma. The distribution of an applied electric field has been shown to be governed by distinct tissue structures and electrical conductivity. Of all the tissues the skull plays a significant role in modifying the distribution of the electric field due to its large impedance. In this study, we studied how remodeling of the skull would affect the therapeutic outcome of TTFields, using a computational approach. METHODS: Head models were created from the head template ICBM152 and five realistic head models. The electric field distribution was simulated using the default TTFields array layout. To study the impact of the skull on the electric field, we compared three cases, namely, intact skull, defective skull, and insulating process, wherein a thin electrical insulating layer was added between the transducer and the hydrogel. The electric field strength and heating power were calculated using the FEM (finite element method). RESULTS: Removing the skull flap increased the average field strength at the tumor site, without increasing the field strength of "brain". The ATVs of the supratentorial tumors were enhanced significantly. Meanwhile, the heating power of the gels increased, especially those overlapping the skull defect site. Insulation lightly decreased the electric field strength and significantly decreased the heating power in deep tumor models. CONCLUSION: Our simulation results showed that a skull defect was beneficial for superficial tumors but had an adverse effect on deep tumors. Skull removal should be considered as an optional approach in future TTFields therapy to enhance its efficacy. An insulation process could be used as a joint option to reduce the thermogenic effect of skull defect. If excessive increase in heating power is observed in certain patients, insulating material could be used to mitigate overheating without sacrificing the therapeutic effect of TTFields.

The dual role of the CD95 and CD95L signaling pathway in glioblastoma.

Binding of CD95, a cell surface death receptor, to its homologous ligand CD95L, transduces a cascade of downstream signals leading to apoptosis crucial for immune homeostasis and immune surveillance. Although CD95 and CD95L binding classically induces programmed cell death, most tumor cells show resistance to CD95L-induced apoptosis. In some cancers, such as glioblastoma, CD95-CD95L binding can exhibit paradoxical functions that promote tumor growth by inducing inflammation, regulating immune cell homeostasis, and/or promoting cell survival, proliferation, migration, and maintenance of the stemness of cancer cells. In this review, potential mechanisms such as the expression of apoptotic inhibitor proteins, decreased activity of downstream elements, production of nonapoptotic soluble CD95L, and non-apoptotic signals that replace apoptotic signals in cancer cells are summarized. CD95L is also expressed by other types of cells, such as endothelial cells, polymorphonuclear myeloid-derived suppressor cells, cancer-associated fibroblasts, and tumor-associated microglia, and macrophages, which are educated by the tumor microenvironment and can induce apoptosis of tumor-infiltrating lymphocytes, which recognize and kill cancer cells. The dual role of the CD95-CD95L system makes targeted therapy strategies against CD95 or CD95L in glioblastoma difficult and controversial. In this review, we also discuss the current status and perspective of clinical trials on glioblastoma based on the CD95-CD95L signaling pathway.

Dynamic nomogram for predicting acute kidney injury in patients with acute ischemic stroke: A retrospective study.

Background: This study sought to develop and validate a dynamic nomogram chart to assess the risk of acute kidney injury (AKI) in patients with acute ischemic stroke (AIS). Methods: These data were drawn from the Medical Information Mart for Intensive Care III (MIMIC-III) database, which collects 47 clinical indicators of patients after admission to the hospital. The primary outcome indicator was the occurrence of AKI within 48 h of intensive care unit (ICU) admission. Independent risk factors for AKI were screened from the training set using univariate and multifactorial logistic regression analyses. Multiple logistic regression models were developed, and nomograms were plotted and validated in an internal validation set. Based on the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) to estimate the performance of this nomogram. Results: Nomogram indicators include blood urea nitrogen (BUN), creatinine, red blood cell distribution width (RDW), heart rate (HR), Oxford Acute Severity of Illness Score (OASIS), the history of congestive heart failure (CHF), the use of vancomycin, contrast agent, and mannitol. The predictive model displayed well discrimination with the area under the ROC curve values of 0.8529 and 0.8598 for the training set and the validator, respectively. Calibration curves revealed favorable concordance between the actual and predicted incidence of AKI (p > 0.05). DCA indicates the excellent net clinical benefit of nomogram in predicting AKI. Conclusion: In summary, we explored the incidence of AKI in patients with AIS during ICU stay and developed a predictive model to help clinical decision-making.

Contralateral subdural effusion after decompressive craniectomy: What is the optimal treatment?

OBJECTIVE: Contralateral subdural effusion after decompressive craniectomy (CSEDC) is rare, and the optimal treatment is not determined. We present 11 cases of CSEDC and give an overview of the English literature pertaining to this disease. METHODS: We searched the database at our institution and performed a search of English literature in PubMed and Google Scholar. Keywords used were as follows (single word or combination): "subdural hygroma"; "subdural effusion"; "decompressive craniectomy". Only patients with CSEDC and contained adequate clinical information pertinent to the analysis were included. RESULTS: 11 cases of CSEDC were recorded at our institution. They comprised ten men and one woman with an average age of 41.9 years. All the 8 symptomatic patients underwent surgery and the CSEDC resolved gradually. 68 cases of CSEDC were found in the literature. Including ours, a total of 79 patients were analyzed. Conservative treatment was effective in the asymptomatic patients. 41.7% of the symptomatic CSEDC underwent burr hole drainage and successfully drained the CSEDC. However, 76% of them received subsequent surgery to manage the reaccumulation of CSEDC. 25% of the symptomatic patients underwent cranioplasty, while 13.3% of them received Ommaya drainage later because of CSEDC recurrence. 18.3% of the symptomatic patients underwent cranioplasty plus subduroperitoneal shunting, and all CSEDC resolved completely. CONCLUSIONS: Burr hole drainage appears to be only a temporary measure. Early cranioplasty should be performed for patients with CSEDC. CSF shunting procedures may be required for patients in whom CSEDC have not been solved or hydrocephalus manifest after cranioplasty.